Keywords
Flavonoids
In silico
Muntingia calabura L
How to Cite
Abstract
In silico methods have been widely acknowledged by researchers as efficient and effective tools for accelerating drug discovery through computer modelling. This study explored the anti-angiogenic potential of flavonoids from Aratiles (Muntingia calabura L.) the first in silico screening of specific flavonoids against a panel of key angiogenic protein receptors, thereby providing a more precise evaluation of its anti-angiogenic potential than previously reported crude extract studies. PyRx software was used to assess each flavonoid ligand's binding score followed by BIOVIA Discovery Studio Visualizer Analysis to determine the binding site, docking pose, binding affinity score, and specific amino acid interactions of each flavonoid ligand within the receptor sites. Out of the forty (40) initial flavonoid ligands, twenty-three (23) were found to comply with Lipinski's Rule of 5, indicating favorable ADME properties (Absorption, Distribution, Metabolism, and Excretion). Using ProTox-3.0-2024 web server, seventeen (17) out of these twenty-three (23) flavonoid ligands have passed the toxicity screening being categorized as Class V- may be harmful and Class VI- non-toxic. The selected flavonoid ligands were then analyzed for their binding affinity to five (5) angiogenic receptors: Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) (Kent, 2012), Fibroblast Growth Factor Receptor 2 (FGFR-2), Transforming Growth Factor Beta Receptor 1(TGF-βR-1), Insulin-like Growth Factor 1 Receptor (IGF-1R), and Endothelial Growth Factor Receptor (EGFR). Ultimately, flavonoid ligand 17 identified as 7-(benzyloxy)-6,8-dimethoxy-5-hydroxyflavone showed strong binding interactions ranging from -9 to -11 kcal/mol for all five (5) angiogenic receptors. These values were almost equal to, and in some instances, higher than those of the control inhibitors. By and large, flavonoid ligand 17 from Aratiles demonstrated a promising anti-angiogenic potential and may serve as a lead compound for further development in anti-cancer therapy.
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